Since 1997 several regional outbreaks of highly pathogenic avian influenza have occurred, and hundreds of cases of avian influenza in humans have been reported. In nearly all confirmed cases, infected persons contracted avian influenza through direct contact with diseased poultry. Although such occurrences remain relatively rare, the persistence of highly virulent H5N1 influenza strains among poultry in Southeast Asia and the high fatality rate (53%) associated with H5N1 infection of humans have engendered concern that a particularly deadly influenza pandemic will develop. For this to occur, one criterion remains to be fulfilled: pandemic influenza must be efficiently transmitted from person-to-person. The barrier preventing such transmission is not well understood; thus, it is difficult to predict how or when currently circulating strains of avian influenza will become competent for propagation within the human population. To address this gap in our understanding, we propose the development of the guinea pig as a mammalian model for influenza virus transmission. For the initial evaluation of influenza infection and disease in guinea pigs, a series of experiments employing well-characterized strains of human influenza are described. A second set of experiments will establish the suitability of guinea pigs for transmission studies in particular, by assessing the efficiency of spread of human influenza viruses between these animals. Three modes of transmission will be examined: contact-, large droplet- and aerosol-based spread. Finally, guinea pigs will be used to compare the transmissibility of several avian and human influenza viruses toward the aim of understanding what characteristics of the virus, and of the disease it causes, are required to support transmission among mammalian hosts. [unreadable] [unreadable] [unreadable] [unreadable]